Antiallergic composition

ABSTRACT

The present invention provides a safe and excellent antiallergic composition, and more particularly a preventive and therapeutic composition for atopic dermatitis, including an antiallergic composition blended with stachyose as an effective ingredient, and a medicine, food and beverage containing the composition.

BACKGROUND OF THE INVENTION

[0001] 1. Field of the Invention

[0002] The present invention relates to an antiallergic composition,particularly to an antiallergic composition usable for daily intake forpreventing onset of atopic dermatitis, and medicines, beverages andfoods using the composition.

[0003] 2. Description of the Related Art

[0004] Allergic diseases such as atopic dermatitis have caused severeproblems in recent years. Atopic dermatitis occurs as dry lichen likeeczema, and is an intractable disease accompanying severe itch. Whilelittle is known about the mechanism of the onset of eczema of the atopicdermatitis, it has been made clear that the disease is related toallergic reactions type I and type IV. A type I allergy is an immediateallergy mainly related to IgE antibodies, wherein chemical transmitterssuch as histamine and leukotriene, and enzymes are released uponreaction of allergenic substances (allergens) with IgE on mast cells andbasophils to cause inflammatory reactions on the skin. However, type Iallergies are considered not to be directly related to lesions of eczemacaused by the atopic dermatitis. A type IV allergy is called as adelayed allergy or cell mediated allergy that causes an inflammatoryreaction related to lymphocytes, and the onset of the disease takes 24to 72 hours after sensitization.

[0005] Many protective and therapeutic actions have been attempted forpreventing atopic dermatitis. Representative examples thereof include(1) an external medication using external medicines such asadrenocortical hormones, and (2) administration of medicines thatsuppress immediate reactions such as antihistamine agents. However, theeffect of medication is not always sufficient depending on the physicalconditions of patents, and the medication has a risk of rebound.

[0006] In addition, people with allergic physical conditions have beenincreasing every year. In extreme examples, the allergic symptom is sosever that daily life of the patient is hindered, which leads to socialproblems. Under these situations, there is an urgency to develop safeand excellent antiallergic medicines to solve the above mentionedproblems, particularly prophylactics and medicaments of the atopicdermatitis.

SUMMARY OF THE INVENTION

[0007] It is an object of the present invention to provide a safe andexcellent antiallergic composition, particularly preventive andtherapeutic compositions of the atopic dermatitis by solving theproblems above on allergic diseases.

[0008] The inventors have found, through intensive studies for attainingthe objects above, that stachyose has an antiallergic action,particularly an action for suppressing atopic dermatitis, and havecompleted the present invention.

[0009] The present invention provides an antiallergic compositioncomprising stachyose as an effective ingredient.

[0010] Stachyose is a tetrasaccharide contained, for example, in soybeans. Stachyose is a hardly digestible oligosaccharide, and has beenknown as a factor for activating Lactobacillus bifidus known to have anintestinal function controlling drug among intestinal bacteria, and foraccelerating absorption of calcium through the digestive intestine.However, the action for suppressing atopic dermatitis as disclosed inthe present invention has not been known in the art.

[0011] While the content of stachyose in the antiallergic composition isnot particularly restricted, a standard of the desirable amount ofintake is 1 to 15 g per day. A content of less than 1 g is not soeffective, while a content of more than 20 g may induce temporarydiarrhea, although it depends on physical conditions.

BRIEF DESCRIPTION OF THE DRAWINGS

[0012]FIG. 1 is a graph showing the scores of dermatitis in thestachyose administration group and control group;

[0013]FIG. 2 is a graph showing the scores of dermatitis in thesaccharose administration group and control group;

[0014]FIG. 3 is photographs of appearances of test mice;

[0015]FIG. 4 is a graph showing the IgE levels in the stachyoseadministration group, and saccharose administration group and controlgroup; and

[0016]FIG. 5 is a graph showing scores of dermatitis in the stachyoseadministration group and conrol group in the conventional NC/Nga mice.

DESCRIPTION OF THE PREFERRED EMBODIMENTS Performance Evaluation Test 1

[0017] The performance of stachyose mixed in livestock feeds wasevaluated against the dermatitis induced by repeated application ofhapten on an NC/Nga mouse frequently used as an atopic dermatitis modelanimal (M. Okada et al., Oyo Yakuri/Pharmcometrics, vol. 59, 135-139(2000)).

Test Method

[0018] NC/Nga Tnd Crj male mice at six weeks of age (purchased fromNihon Charles River) were habituated for two weeks. The animals decidedas healthy were used for the experiments after an observation of generalconditions and body weight measurement. The mice were divided into threegroups so that the body weight was averaged One group was composed ofnine mice. A purified livesock feed (AIN93G produced by Oriental YeastCo.) was used as a basic feed.

[0019] The mice in Group 1 (a control group) was fed with the purifiedfeed, while the mice in Groups 2 and 3 were fed with a feed prepared byadding the test samples as shown in Table 1 in the basic feed. TABLE 1Group 1 AIN93G feed Group 2 AIN93G feed + stachyose 0.5% Group 3 AIN93Gfeed + saccharose 0.5%

[0020] Stachyose used in this test was purified to a purity of 98% byion exchange chromatography after extracting from soybeans with 70%ethanol. Saccharose used in this test was purchased from Wako JunyakuKabushiki Kaisha.

[0021] The mice at eight weeks of age were used for sensitization asfollows. The abdomen of the mouse anesthetized with ether was clippedwith a pair of hair clippers and a solution of2,4,6-trinitrochlorobenzene (named as picryl chloride (PiCl)hereinafter) for sensitization was applied on the abdomen after clippingand on the footpad in a proportion of 150 μL/one animal. Induction wasstarted four days after sensitization, and repeated once a week for fiveweeks. In the induction period, the back of the mouse anesthetized withether was clipped with a pair of hair clippers, and the PiCl solution(150 μL/one animal) was applied on the clipped back and right and leftears (at the outer and inner sides of each ear). The hair was clippedafter the second induction depending on the growth of the hair.

[0022] The symptoms of the atopic dermatitis were observed as follows.The skin condition was observed twice a week starting from a day beforethe first induction, and the following items were evaluated based on thecriteria of clinical syndromes of the human atopic dermatitis. Eachmouse was photographed on the day of autopsy.

[0023] (1) Observed items

[0024] a. pruritus/itching

[0025] b. erythema/hemorrhage

[0026] c. edema

[0027] e. excoriation/erosion

[0028] f. scaring/dryness

[0029] (2) Evaluation point

[0030] 0 no syndrome

[0031] 1 mild syndrome

[0032] 2 intermediate syndrome

[0033] 4 severe syndrome

[0034] The serum total IgE concentration was measured as follows. Theblood was extracted on day four before administration, and on 43rd dayafter administration (the day for starting administration is counted asthe first day). The blood (200 μL) is sampled from the orbital plexusvenosus using a heparinated capillary. The blood sampled was placed in atube, centrifuged (at about 4° C. and 1660 g for 15 minutes), and IgE inthe supernatant was used for the serum total IgE measurement by anenzyme-linked immunosorbent assay (EIA).

[0035] The score of dermatitis, serum total IgE concentration, and theaverage body weight and standard deviation thereof were calculated. Thesignificant difference was evaluated by the student's test. Asignificance level of 5% was evaluated as significant, and the resultsof the Students t-test were expressed by dividing into a level of lessthan 5% (P<0.05) and less than 1% (P<0.01).

Results and Discussion

[0036] The data of the score of dermatitis are shown in FIGS. 1 and 2.As shown in FIG. 1, progress of the atopic dermatitis was evidently bredin the stachyose administration group (Group 2). No effects wereobserved in the saccharose administration group (Group 3) as shown inFIG. 2. The photograph of the appearance of a representative mouse ineach group is shown in FIG. 3. An evident difference of the appearanceof the skin was observed in the mouse in the stachyose administrationgroup as compared with the mouse in the control group (Group 1).

[0037] The levels of the serum total IgE as an immediate type (type I)allergy inducing substance are shown in FIG. 4. These levels were notdifferent from the level in the control group.

[0038] While the expression mechanism of the anti-atopic dermatitisaction of stachyose has not been made clear yet, it may be conjecturedthat stachyose probably acts on intestinal microorganisms to improveimmunity of the digestive intestine. Otherwise, stachyose may directlyact on the cells related to immunity of the digestive intestine. Whilethe atopic dermatitis is considered to be related to the immediateallergy and delayed allergy (type IV), it was made clear from theresults of the present invention that stachyose has a function againstthe delayed allergy since stachyose does not influence the level of IgE.While it is known in the art that raffinose as a minute component of thesoy bean oligosaccharide has an ant-atopic dermatitis action (JapanesePatent Application Laid-open No. Hei 11-255656), raffinose has an actionfor suppressing production of IgE (Japanese Patent Application Laid-openNo. 2001-288093). Accordingly, the action of stachyose shown in thepresent invention is evidently different from the action of raffinose.

Performance Evaluation Test 2

[0039] The effect of stachyose on the dermatitis was investigated usingconventional grade NC/Nga mice that spontaneously start the atopicdermatitis without applying any haptens (H. Matsuda et al.,International Immunology, vol. 9. 461-466 (1997)).

Test Method

[0040] Conventional grade female NC/Nga mice at four weeks of age(purchased from Nihon SLC) were habituated for one week The mice weredivided into two groups so that the body weight was averaged. One groupwas composed of six mice. All the mice were freely fed on the purifiedlivestock feed (AIN93G) before grouping, and the stachyoseadministration group was fed on a feed supplemented with 1% stacyoseafter grouping. The sldn conditions were observed and evaluated once pertwo weeks from the day of start of grouping. The evaluation method wasthe same as in performance evaluation method 1.

Results

[0041] While the dermatitis was observed on the face of five of six micein the control group on the week four after grouping, no onset of thedermatitis was observed in the stachyose administration group. Whileevident dermatitis was observed not only on the face but also on theears in the control group 6 to 8 weeks after grouping, no onset ofdermatitis was observed at all in the stachyose administration group.The scores of dermatitis are shown in FIG. 5. The scores of dermatitisshow that the effect of stachyose is evident

[0042] The origin and production method of stachyose used in the presentinvention are not particularly rested, and any one of natural stachyose,chemically synthesized stachyose and enzymatically synthesized stachyosemay be used. However, stachyose originating from soy beans iseconomically advantageous. Since stachyose is a principal ingredient ofthe soybean oligosaccharide, the oligosaccharide may be direly used asthe stachyose source, or it may be used after purification by ionexchange chromatography.

EXAMPLES

[0043] While the present invention is described with reference toexamples, the present invention is by no means restricted by theexamples as set forth below.

Example 1

[0044] [Ingredient of Capsule] Starting Material Blend (mg) per 1Capsule (1) Stachyose 50 (2) DHA Oil 50 (3) Beefsteak Plant Oil 50 (4)Bee Wax 50

[0045] These materials were capsulated using gelatin after mixing.

Example 2

[0046] [Tablet] Starting Material Blend (mg) per 1 Capsule (1) Stachyose100 (2) Lactose 100 (3) Cellulose Powder 50 (4) Reduced Maltose 30 (5)Processed Starch 10 (6) Calcium Carbonate 1

[0047] These materials were formulated into tablets after mixing.

Example 3

[0048] [Beverage] Starting Material Blend (g) per 1 Bottle (1) Soy BeanOligosaccharide (Stachyose 50%) 2 (2) Sucrose 10 (3) Coffee Powder 5 (4)Cow Milk 183

[0049] Beverage supplemented with soy bean oligosaccharide and stachyosewas produced with sterilization after mixing.

[0050] It is evident that the composition blended with stachyose of thepresent invention exhibits an atopic dermatitis suppressing effect.

What is claimed is:
 1. An antiallergic composition comprising stachyoseas an effective ingredient.
 2. The antiallergic composition according toclaim 1, wherein the stachyose is originated from soybeans.
 3. Theantiallergic composition according to any one of claims 1 and
 2. whereinan antiallergic function is an action for suppressing atopic dermatitis.4. The antiallergic composition according to any one of claims 1 to 3,wherein the antiallergic function is an action for suppressing a delayedallergy.
 5. A medicine, and beverage and food comprising theantiallergic composition according to any one of claims 1 to 4.